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Microfluidic tools and techniques for manipulating fluid droplets have become core to many scientific and technological fields. Despite the plethora of existing approaches to fluidic manipulation, non-Newtonian fluid phenomena are rarely taken advantage of. Here we introduce embedded droplet printing-a system and methods for the generation, trapping, and processing of fluid droplets within yield-stress fluids, materials that exhibit extreme shear thinning. This technique allows for the manipulation of droplets under conditions that are simply unattainable with conventional microfluidic methods, namely the elimination of exterior influences including convection and solid boundaries. Because of this, we believe embedded droplet printing approaches an ideal for the experimentation, processing, or observation of many samples in an "absolutely quiescent" state, while also removing some troublesome aspects of microfluidics including the use of surfactants and the complexity of device manufacturing. We characterize a model material system to understand the process of droplet generation inside yield-stress fluids and develop a nascent set of archetypal operations that can be performed with embedded droplet printing. With these principles and tools, we demonstrate the benefits and versatility of our method, applying it toward the diverse applications of pharmaceutical crystallization, microbatch chemical reactions, and biological assays.
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Non-spherical hydrogel particles are of fundamental interest and can find use in a variety of applications ranging from pharmaceuticals to biomedical to food. Here, we report a new method that leverages the yield stress property of viscoplastic fluids to synthesize shape-engineered alginate particles. By dripping an aqueous viscoplastic solution composed of sodium alginate and a yield-stress material into an ionic gelation bath, droplets are controllably deformed and crosslinked, producing a wide assortment of shapes. We find that by tuning the yield stress of the solution and the nozzle tip orientation, a range of shapes from symmetric and near-spherical, to asymmetric and anisotropic (e.g., egg-, rice grain-, arc-, ring-, snail shell-, tear-, and tadpole-like) can be produced. We explain our observations using scaling analysis of the forces exerted on the droplet at different stages of particle production. We show that the main factors that determine the degree of droplet deformation during bath entry and the final appearance of the alginate particles are the initial shape of the droplets, the timescales of the viscoplastic fluid relaxation versus the crosslinking reaction, and the physico-chemical properties of the yield-stress material.
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Alginatos , Hidrogeles , Alginatos/química , Hidrogeles/química , IonesRESUMEN
We demonstrate that small unidirectional applied-stresses during temperature-induced gelation dramatically change the gel temperature and the resulting mechanical properties and structure of aqueous methylcellulose (MC), a material that forms a brittle gel with a fibrillar microstructure at elevated temperatures. Applied stress makes gelation more difficult, evidenced by an increased gelation temperature, and weakens mechanical properties of the hot gel, evidenced by a decreased elastic modulus and decreased apparent failure stress. In extreme cases, formation of a fully percolated polymer network is inhibited and a soft granular yield-stress fluid is formed. We quantify the effects of the applied stress using a filament-based mechanical model to relate the measured properties to the structural features of the fibril network. The dramatic changes in the gel temperature and hot gel properties give more design freedom to processing-dependent rheology, but could be detrimental to coating applications where gravitational stress during gelation is unavoidable.
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PURPOSE: Industrial implementation of continuous oral solid dosage form manufacturing has been impeded by the poor powder flow properties of many active pharmaceutical ingredients (APIs). Microfluidic droplet-based particle synthesis is an emerging particle engineering technique that enables the production of neat or composite microparticles with precise control over key attributes that affect powder flowability, such as particle size distribution, particle morphology, composition, and the API's polymorphic form. However, the powder properties of these microparticles have not been well-studied due to the limited mass throughputs of available platforms. In this work, we produce spherical API and API-composite microparticles at high mass throughputs, enabling characterization and comparison of the bulk powder flow properties of these materials and greater understanding of how particle-scale attributes correlate with powder rheology. METHODS: A multi-channel emulsification device and an extractive droplet-based method are harnessed to synthesize spherical API and API-excipient particles of artemether. As-received API and API crystallized in the absence of droplet confinement are used as control cases. Particle attributes are characterized for each material and correlated with a comprehensive series of powder rheology tests. RESULTS: The droplet-based processed artemether particles are observed to be more flowable, less cohesive, and less compressible than conventionally synthesized artemether powder. Co-processing the API with polycaprolactone to produce composite microparticles reduces the friction of the powder on stainless steel, a common equipment material. CONCLUSIONS: Droplet-based extractive solidification is an attractive particle engineering technique for improving powder processing and may aid in the implementation of continuous solid dosage form manufacturing.
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Antimaláricos/química , Arteméter/química , Excipientes/química , Técnicas Analíticas Microfluídicas , Poliésteres/química , Cristalización , Composición de Medicamentos , Emulsiones , Fricción , Polvos , ReologíaRESUMEN
We describe the 3-iodopropyl acetal moiety as a simple cleavable unit that undergoes acid catalyzed hydrolysis to liberate HI (p Ka â¼ -10) and acrolein stoichiometrically. Integrating this unit into linear and network polymers gives a class of macromolecules that undergo a new mechanism of degradation with an acid amplified, sigmoidal rate. This trigger-responsive self-amplified degradable polymer undergoes accelerated rate of degradation and agent release.
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We present a paradigm for the design of yield-stress fluids, using six archetypal materials for demonstration. By applying concepts of engineering design, we outline a materials design paradigm that includes (i) morphological organization based on jammed versus networked microstructures, (ii) collected scaling laws for predictive design, (iii) low-dimensional descriptions of function-valued flow data, (iv) consideration of secondary properties including viscous behavior, and (v) a strategy for material concept synthesis based on the juxtaposition of microstructures. By explicitly specifying these design strategies, we seek to create an ontology and database for the engineering of yield-stress fluids. Our proposed design strategy increases the likelihood of finding an optimal material and prevents design fixation by considering multiple material classes to achieve a desired rheological performance. This flips the typical structure-to-rheology analysis to become the inverse: rheology-to-structure with multiple possible materials as solutions.
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Reversible transformations in bulk polymers offer numerous possibilities for materials remodeling and reprocessing. While reversible systems based on dynamic covalent chemistry such as the Diels-Alder reaction and transesterification have been intensively studied to enable local bond dissociation and formation, reports regarding the reversion from bulk network polymers to monomers are rare. Herein, we report a reversibly polymerizable system based on ring-opening metathesis polymerization of cyclopentene derivatives in the bulk state. The network polymer is thermodynamically stable and mechanically robust at room temperature and readily depolymerizes at elevated temperatures to yield liquid monomers that are repolymerized to cross-linked polymers by simply cooling to room temperature. This reversible process was characterized by differential scanning calorimetry and rheological tests.